In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer ⁶⁸Ga-NODAGA-Procainamide (PCA)

The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel ⁶⁸Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques.

Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 (⁶⁸Ga-NODAGA-PCA). The melanin specificity of ⁶⁸Ga-NODAGA-PCA was tested in vitro, ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for ⁶⁸Ga-NODAGA-PCA and ¹⁸FDG tracers.

⁶⁸Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that ⁶⁸Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly (p≤0.01) higher ⁶⁸Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where ¹⁸FDG and ⁶⁸Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly (p≤0.05 and p≤0.01) higher using ⁶⁸Ga-NODAGA-PCA than the ¹⁸FDG accumulation.

Our novel radiotracer ⁶⁸Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, ⁶⁸Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo.